Switching to Adalimumab has proven to be efficacious in Crohn's disease (CD) patients with intolerance or loss of response to Infliximab. Currently there are no studies on the efficacy of switching to Infliximab in patients with loss of response or primary non-response to Adalimumab. Even in rheumatology, where switching between all classes of anti-TNFα biologicals is common practice, there are no scientific data on switching from humanized to chimeric anti-TNFα antibodies.

The purpose of this study is to document the efficacy of such a switch and to identify the possible predictive factors for success.

If treatment with Adalimumab fails (despite optimal dose and interval) and the treating physician therefore decided to switch to infliximab, the patient may be enrolled in this observational study. At regular intervals (every Remicade), the patient will be clinically re-evaluated. The disease activity score will be calculated: Crohn's disease activity index (CDAI). At regular intervals, the results of interim blood tests will be documented (3x). The succession will be 1 year. At week 10, 26 and 52, additional serum samples will be taken for determination of antibodies against Adalimumab and Infliximab. The serum levels of Adalimumab (week 0) and Infliximab (week 10, 26 and 52) will be determined.

For this study there is no specific therapy change. The study wants only to document the results of a therapy switch that, in current clinical practice, is made by the treating physician.

Assess efficacy of switching from Adalimumab to Infliximab. [ Time Frame: after 10 weeks ] [ Designated as safety issue: No ]

The primary objective of the study is to assess the efficacy of switching to Infliximab for the induction of clinical remission in subjects with moderately to severely active Crohn's disease with primary non-response or loss of response to Adalimumab.

The proportion of subjects achieving clinical remission at week 10 after 3 infusions of Infliximab (week 0, 2 and 6). Clinical remission is defined as a total Crohn's Disease Activity Index (CDAI) score of 150 or less.

To assess the efficacy of switching from Adalimumab to Infliximab for the induction of clinical response. The proportion of subjects with clinical response (at least 70 point decrease in Crohn's Disease Activity Index (CDAI)) at week 10.

To assess the efficacy of switching from Adalimumab to Infliximab to achieve sustained clinical remission, treating with maintenance Infliximab infusions, without the need for Infliximab therapy optimization (interval shortening or dose increase).

The proportion of subjects with sustained clinical remission (CDAI 150 or less) at weeks 26 and 52, without the need for Infliximab therapy optimization (interval shortening or dose increase).

To assess the treatment failure of switching from Adalimumab to Infliximab. The proportion of patients with treatment failure. Failure is defined as cessation of Infliximab due to intolerance or insufficient efficacy despite therapy optimization or the start or dose increase of any other Crohn's disease medication during the study (including corticosteroids, immunosuppressants and 5-aminosalicylic acid (5-ASA) analogues).

Tolerance and safety for switching from Adalimumab to Infliximab. [ Time Frame: After 10, 26 and 52 weeks. ] [ Designated as safety issue: Yes ]

Adverse events/Serious adverse events will be analysed. Hematology and biochemistry will be analysed at weeks 10, 26 and 52.

Serological factors associated with switching from Adalimumab to Infliximab. [ Time Frame: after 10, 26 and 52 weeks ] [ Designated as safety issue: No ]

C-Reactive Protein (CRP) at screening, weeks 10, 26 and 52.

Antibodies to Adalimumab at baseline, weeks 10, 26 and 52.

Trough level of Adalimumab at baseline.

Antibodies to Infliximab at weeks 10, 26 and 52.

Trough level of Infliximab at weeks 10, 26 and 52.

Biospecimen Retention: Samples Without DNA

At regular intervals, the results of interim blood tests will be documented (3x).

After 10, 26 and 52 weeks, additional serum samples will be taken for determination of antibodies against Adalimumab and Infliximab. The serum levels of Adalimumab (week 0) and Infliximab (week 10, 26 and 52) will be determined.

stable dose for 2 weeks prior to baseline, then tapering at the discretion of the investigator.

Immunosuppressants (azathioprine, 6-mercaptopurine, methotrexate):

patients taking this medication prior to baseline: stable dose for 8 weeks prior to baseline, then stable dose until week 26 of the study. Starting or restarting of immunosuppressants is allowed until week 2, then stable dose until week 26 of the study.

Adalimumab: at least 2 week washout period prior to first Infliximab infusion.

Starting or increasing the dose of other medication for Crohn's disease than Infliximab during the study will be considered as "treatment failure". (except for immunosuppressants as described above under 2.)

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01338740